This Career Development Award application describes an integrated training and research program for Michael Silverberg, Ph.D., MPH designed to provide expertise in the topic of cancers in an aging HIV-infected population. Dr. Silverberg's interests in the viral etiology of cancers, focusing on human papillomavirus, as well as the benefits and consequences of long-term highly-active antiretroviral therapy (HAART) use, have shaped his commitment to the study of cancers in HIV patients, which account for one-third of deaths in this group. Three retrospective cohort studies are proposed using laboratory, pharmacy and clinical databases of Kaiser Permanente, and include 18,000 HIV-infected and 180,000 HIV-uninfected persons followed from 1996 to 2006. These research projects aim to: 1) compare cancer incidence by HIV status and HAART use;2) compare cancer progression by HIV status and HAART use;and, 3) identify adverse events associated with concomitant HAART use and cancer therapy. Study strengths include the large size, individual data on HAART and traditional cancer risk and prognostic factors, stable and extended follow-up, precise linking of disease registries, and inclusion of HIV-uninfected controls. Career goals that will be achieved during the award period are: 1) acquiring expertise in cancer epidemiology and biology;2) attaining proficiency in advanced biostatistical methods;3) obtaining knowledge of clinical management of HIV and cancer;and 4) developing academic and professional skills. The tradition of outcomes-oriented research at the Division of Research at Kaiser Permanente, supplemented by the resources at several academic institutions provide the ideal environments to achieve these goals. A strong team of mentors has been assembled to provide diverse expertise in cancer etiology, epidemiology, biostatistics and clinical care. These skills are essential for the multidisciplinary environment of Kaiser Permanente. Career goals will also be met through coursework, directed reading, focused biostatistics training, clinic observations, attendance at conferences and workshops, and through research. It is not known why cancer risk is increased among HIV-infected patients or why prognosis is often worse. It is also not known which cancers are affected by long-term HAART use or if simultaneous HAART use and cancer therapy is associated with side effects. The results of this research may be informative to those providing care to HIV-infected patients with or at-risk for cancer.